The normal flora of the oral cavity is composed of many types of aerobic, facultatively anaerobic and obligately anaerobic microorganisms represented by Streptococci and Actinomyces; Neisseria and Nocardia; Veillonella and Fusobacterium, respectively. The former are found almost exclusively on the oral mucosa; the latter two groups are found predominantly in subgingival (beneath the gum line) habitats. For instance Streptococci colonize on the surfaces of the teeth secondary to plaque formation; plaque serves as a substrate, both in a mechanical sense and in a biological sense.
It is well known that mammalian teeth are vulnerable to degradation from the cariogenic manifestations of bacterial exudates, i.e., caries. Caries, in effect, result from the disintegration of tooth substance beginning at the exterior surface and progressing inwardly. Initially, the surface enamel of teeth, which is entirely non-cellular, is demineralized. Basically, this is attributed to the effect of acid products of either bacterial fermentation or saliva or both. Subsequent to the demineralization of the surface enamel, the dentin and cementum are decomposed generally from bacterial digestion of the protein matrix.
The essential first step in caries production appears to be due to the formation of plaque on the hard, smooth enamel surface of the dentition. Chitinoid structures are found bound tightly to the surfaces of mammalian dentition both supra and subgingivally in the form of plaque. Such plaque is highly resistant to chemical attack, being generally removable only by abrasive means, and can serve as a nutritional source for bacterial species. The essential second step in caries production appears to be due to the formation of large amounts of acid from either bacteria or saliva or both. Unfortunately, large concentrations of acid as aforesaid demineralize the adjacent enamel to initiate the formation of caries.
Plaque is often referred to as "bacterial plaque"; in fact, large numbers of bacterial species can be isolated from plaque deposits by usual culture techniques. Generally, it is theorized that plaque consists of a polymerized form of sialic acid, the origin of which is saliva. Sialic acids are acetyl derivatives of neuraminic acid. (These serve as monomers which, under conditions of acidified environments can easily polymerize). In the salt form, at basic pH ranges, they are relatively soluble, lending thixatropy to the saliva. Mucoid materials contain, often times, these and similar substances which give them a slippery feeling. Acid formed by bacterial activity on, for instance, carbohydrates tend to acidify the oral cavity to an abnormally low pH range. This tends to cause the neuramic acid derivatives to polymerize and there appears to be a chemical bond effected between the normal hydroxyapatite structure of the teeth and the polymerized neuraminic acid. Therefore, there exists a suitable enzymatic substrate in juxtaposition to a normal biological structure, a condition which can lead to the secondary enzymatic alteration of the desirable structure. Such activity is evidenced by caries formation.
It is well known that the periodic removal of plaque from dental enamel reduces the occurrence of caries. Furthermore, it is well known that the use of preparations containing available fluoride anions imparts anticaries protection to the dental surfaces, presumably by the insertion of fluoride ions into the structure of the hydroxyapatitie via substitution of or combination with the hydroxyl groups giving rise to the theoretical structures fluoroapatite or fluorohydroxyapatite. Such structures appear to be much less susceptible to the cariogenic activities of bacterial exudates which are composed of, among other entities, toxins and similar substances with enzymatic activity. That is, where such enzymatic activity might readily degrade the hydroxyapatite and its associated phosphate groups, the insertion of fluoride appears to render the structures far less susceptible to enzymatic degradation. Thus, caries formation is markedly reduced, as has been pragmatically documented, since the introduction of intentional water fluoridation and the use of dentifrices containing fluoride anions.
Therefore, there are two basic methods which are presently used concurrently as means to effectively reduce the formation of caries as a result of the activity from the normal bacterial flora present in the oral cavity. The first and less frequent method is a physical method which involves mechanical removal of the plaque from the surfaces of the teeth, since plaque is relatively resistant to chemical attack. The second and more frequent method is a chemical method to be conducted on a frequent or even daily basis which is concerned with chemically altering or mineralizing the normal hydroxyapatite structures of teeth to fluoroapatite or fluorohydroxyapatite with, for instance, fluoride containing dental compositions. Basically, the incorporation of fluoride into dental structures apparently renders teeth more resistant to enzymatic degradation thereby reducing the formation of caries.
In addition to the use of fluoride in aiding of the arrest of the caries process, several dental preparations have been heretofore formulated which have utilized divalent metals such as copper, chromium, cobalt and zinc as alternative dietary fortification means. Examples of such dental preparations can be found in U.S. Pat. Nos. 4,375,460, 4,339,429, 4,332,791, 4,235,633, 4,048,300 and U.S. Pat. No. 2,154,168. Unfortunately, the divalent metal complexes disclosed in the above listed U.S. patents and incorporated into those dental preparations have been generally heretofore unsatisfactory. For instance, virtually all of those divalent metal complexes presently utilized are relatively insoluble in aqueous media. In addition to the disadvantage of insolubility, such divalent metal complexes are so stable at the pH ranges generally encountered in the oral cavity that only slight amounts of metal ions dissociate rendering them relatively ineffective. Moreover, because of the stability factor, generally larger quantities of the divalent metal complexes have to be incorporated into those dental preparations which adversely affect the overall taste and mouth feel of the final products.
With respect to the subgingival structures, this situation differs somewhat in that anaerobic bacterial flora appear to preferentially attack soft tissue vis-a-vis the apatite components. Periodontal ligaments bind the tooth to the bony structure of the jaws not unlike the ligamentous structures associated with the normal musculoskeletal junctures. These periodontal ligaments appear to be highly susceptible to enzymes secreted by the anaerobic species found subgingivally. The gradual decomposition of both the ligamentous and bony structures eventually leads to the ultimate loss of attachment of the teeth to the bone. This unfortunately can result in infection, sinus tract formations, subgingival and pericoronal abscess formation and ultimate tooth loss.
In summary, previous attempts or approaches have been made to formulate suitable dental compositions for mineralizing teeth to prevent or reduce caries. Heretofore no satisfactory dental compositions other than those containing fluoride anions have been developed which can overcome the problems aforementioned. Basically, the types of known divalent metal complexes fall into two undesirable categories: those in which cations are normally found very tightly bound to counter ions, and those found in an insoluble form as hydrous oxides of the metal.
In other words, all of the dental compositions utilizing divalent metal complexes other than fluoride provided hitherto invariably and necessarily lack some of the key fundamental properties required to provide sufficient amounts of therapeutic metal ions in the oral cavity. Consequently, there are strong dental and commercial needs for dental compositions containing metal complexes suitable for mineralizing dental structures to reduce or prevent the decay of dental structures.